Biomedical subjects
Publications and source records attributed to T Tsuda.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Fundamental and clinical studies were performed on a newly developed carbapenem antibiotic, imipenem/cilastatin sodium (MK-0787/MK-0791), and results were summarized as follows. The antibacterial activity of MK-0787 at an inoculum of 10(6) cells/ml against strains of S. aureus which were sensitive or resistant to cefazolin (CEZ), E. coli, P. mirabilis, K. pneumoniae, S. marcescens and P. aeruginosa were determined and compared with activities of ceftazidime (CAZ), CEZ, cefmetazole (CMZ), ceftizoxime (CZX), latamoxef (LMOX), cefamandole (CMD), cefoperazone (CPZ), cefsulodin (CFS) and piperacillin (PIPC). The peak MIC of MK-0787 was less than or equal to 0.024 micrograms/ml against S. aureus, which were sensitive or resistant to CEZ, 0.10 micrograms/ml against E. coli, P. mirabilis, or K. pneumoniae, 0.39 micrograms/ml against S. marcescens and 1.56 micrograms/ml against P. aeruginosa. The antibacterial activity of MK-0787 against these bacteria was, on the whole, superior to that of CAZ, CEZ, CMZ, CZX, LMOX, CMD, CPZ, CFS or PIPC. The pharmacokinetics of MK-0787/MK-0791 was studied in 10 children at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg by a 30-minute intravenous drip infusion. Maximum serum levels of MK-0787, at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg were 41.6 micrograms/ml and 72.9 micrograms/ml, respectively, at the end of infusion and 0.1 micrograms/ml at 6 hours, respectively, after drip infusion. The half-life of both dose levels was 0.9 hour. Mean peak serum levels of MK-0791, at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg, were 49.7 micrograms/ml and 87.0 micrograms/ml, respectively, with half-life of 1.1 and 0.6 hour, respectively. Urinary recovery rates of MK-0787 for 6 hours at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg, were 47.8-82.7% and 25.5-78.0%, respectively, and of MK-0791 for 6 hours were 51.7-93.4% and 40.3-94.4%, respectively. Twenty-four patients, including 1 with purulent meningitis, 1 with septicemia, 1 with pyothorax, 10 with bronchopneumonia, 7 with pyelonephritis and 4 with infections of cutaneous soft tissue were treated with MK-0787/MK-0791 at dose levels of over 100 mg/100 mg/kg/day with purulent meningitis and septicemia and 28.8 mg/28.8 mg-72.8 mg/72.8 mg/kg/day with other infections. The clinical response in all patients was excellent or good.(ABSTRACT TRUNCATED AT 400 WORDS)
Explore the source record for details and available documents.
As a new method for regional wall motion analysis, the tomographic functional images, including "coronal", "sagittal" and "four-chamber" sections, were produced by applying the fundamental Fourier analysis using gated cardiac pool emission computed tomography (POOL-SPECT). Segmental wall motion was qualitatively assessed from the functional images in 10 normal subjects and in 48 patients with myocardial infarction. The results were compared with those assessed by gated blood pool planar images (modified LAO 45), two-dimensional echocardiography (2DE) or contrast left ventriculography (LVG). The following results were obtained. 1. POOL-SPECT imaging could separate the ventricle in three dimensions from the neighboring cardiovascular system by avoiding the overlapping blood pool to make accurate recognition of regional wall motion. 2. The functional tomograms had greater clinical efficacy in the diagnosis of infarcted segments than did the conventional equilibrium method, with high sensitivity (93/99, 93.9%), specificity (128/141, 90.8%) and accuracy (221/240, 92.1%), especially in the apical and inferoposterior portions. 3. Tomographic functional imaging facilitated estimating segmental cardiac performance from spatial and temporal aspects. The amplitude image which expresses regional stroke volume was readily available to detect hypokinesis and akinesis. The phase image of the initial cardiac movement was very useful for diagnosing dyskinesis. 4. In comparing the qualitative analysis with 2DE or LVG, complete agreement was observed in 80% (128/160) and 85.1% (149/175) of segments, though POOL-SPECT imaging showed underestimations in 11% of the segments. In conclusion, POOL-SPECT can be performed repeatedly without potential risks and the tomographic functional images derived from application of Fourier analysis to POOL-SPECT images are very useful for qualitative and three-dimensional analysis of regional wall motion. Thus, this technique may be a promising procedure in clinical investigations, obviating the disadvantages of conventional methods.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The total number women examined by the screening car staff from 1974 to 1983 was 120,860. The number of people examined increased from 3.9% in 1974 to 6.2% in 1983, but is still low. The percentage of people requiring detailed examination was 0.77%-2.02%, and the rate of those, actually examined in detail was 86.3%-97.7%. The rate of detection of carcinoma was 0.08-0.3%. The ratio of dysplasia, CIS and invasive carcinoma was 1.3:1.7:1.0 in the first half of the 1974-78 period and changed to 6.1:2.5:1.0 during the 5 years from 1979 to 1983. Regarding the number of examinations required before detecting CIS and invasive carcinoma, all subject with a more advanced than stage Ib carcinoma of the cervix uteri were detected at the time of the initial examination. As to stage Ia of carcinoma of the cervix, 3 out of 31 subjects were detected at the second visit, 28 subjects at the first visit; 126 out of 146 subjects with CIS at the first visit, and 6 at the third visit or later. The results of cytodiagnosis were, in 72 cases of the class IV, dysplasia was found in 8.7%, CIS in 56.9%, invasive carcinoma in 12.1%, false positive in 22.2%, while in 51 cases of class V, dysplasia was found in 1.9%, CIS in 45.1%, invasive carcinoma 47.1% and false positive in 5.8%. CAI in Fukui Prefecture calculated as the sum of clinic and automobile health examinations, was 152 in 1982, 148 in 1983, 177 in 1984.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In human washed platelets, collagen-induced phosphoinositide turnover was inhibited by indomethacin, an inhibitor of thromboxane A2 (TXA2) formation, particularly at lower doses of collagen. This inhibition was counteracted by the addition of 9,11-epithio-11,12-methano-TXA2 (STA2), a stable analogue of TXA2 as well as by the Ca2+ ionophore A23187. STA2 and A23187 did not stimulate phosphoinositide turnover markedly, but significantly increased cytoplasmic free Ca2+ concentrations. The actions of STA2 were blocked by 13-azaprostanoic acid, a TXA2 receptor antagonist. The results suggest that TXA2 is generated during the action of collagen and increases cytoplasmic free Ca2+ which then stimulates phosphoinositide turnover in cooperation with collagen.
Addition of fibroblast growth factor (FGF) to quiescent cultures of Swiss 3T3 cells rapidly induced diacylglycerol formation, protein kinase C activation and Ca2+ mobilization. Protein kinase C-activating agents such as 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1-oleoyl-2-acetylglycerol (OAG) mimicked the action of FGF and stimulated DNA synthesis in the presence of insulin. Prolonged treatment of the cells with phorbol-12,13-dibutyrate (PDBu) led to the down-regulation and complete disappearance of protein kinase C. In these cells, TPA and OAG did not induce DNA synthesis any more. FGF still elicited Ca2+ mobilization and DNA synthesis, but the magnitude of DNA synthesis was reduced to almost half as compared with that in the control cells. These results clearly indicate that both diacylglycerol and Ca2+ may serve as second messengers for FGF and suggest that these messengers may be involved in the mitogenic action of this growth factor.
Addition of platelet-derived growth factor (PDGF) to quiescent cultures of Swiss 3T3 fibroblasts rapidly increased the cytoplasmic free Ca2+ concentrations and afterwards the c-myc mRNA levels. The concentrations of PDGF needed for both reactions were roughly the same. Moreover, the Ca2+ ionophores, A23187 and ionomycin, mimicked the actions of PDGF and increased the c-myc mRNA levels. These results suggest that Ca2+ may be involved in the regulation of PDGF-induced expression of the c-myc gene.
Many extracellular signals elicit Ca2+ mobilization and diacylglycerol formation in their target cells. Diacylglycerol is derived from the receptor-linked phosphoinositide turnover and serves as a second messenger for the activation of protein kinase C in the presence of Ca2+ and phosphatidylserine. Unique diacylglycerols such as 1-oleoyl-2-acetyl-glycerol, which activate intracellular protein kinase C when added to intact cells, have been synthesized. Tumor-promoting phorbol esters substitute for such diacylglycerols and directly activate protein kinase C in both intact cell and cell-free systems. Under appropriate conditions, the synthetic diacylglycerols and phorbol esters induce protein kinase C activation without Ca2+ mobilization, whereas Ca2+ ionophore A23187 induces Ca2+ mobilization without protein kinase C activation. Using these substances, we have obtained evidence that both protein C and Ca2+ are involved in and play a synergistic role in exocytosis, cell division, and other cellular functions. In this article, the role of protein kinase C in transmembrane signaling is discussed.